BACKGROUND:Our previous study found that Modified Erxian Pill could alleviate inflammation in collagen-induced arthritis rats,but its mechanism needs to be further verified. OBJECTIVE:To analyze the components absorbed in the blood of Modified Erxian Pill,and observe the effect of the drug-containing serum of Modified Erxian Pill on pyroptosis of J774A.1 macrophages. METHODS:(1)Analysis of components absorbed in the blood of Modified Erxian Pill:Ultra-high performance liquid chromatography-high resolution mass spectrometry was used to detect and identify Modified Erxian Pill and its components absorbed in the blood.(2)Effect of the drug-containing serum of Modified Erxian Pill on pyroptosis of J774A.1 macrophages:Molecular docking technology was used to initially verify the sesquiterpenoids and NLRP3 in components absorbed in the blood of Modified Erxian Pill.J774A.1 macrophages were randomly divided into blank control group,lipopolysaccharide+adenosine triphosphate group,and lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill with low(2.5%),medium(5%),and high(10%)dose groups.The release of lactate dehydrogenase in the cell supernatant of each group was detected according to the kit instructions.The levels of interleukin-1β and interleukin-18 in cell supernatant were detected in each group by ELISA.The cell membrane damage was detected by Hoechst/PI staining.The expression levels of NLRP3,Caspase-1,GSDMD,and GSDMD-N protein in the cells of each group were detected by western blot assay. RESULTS AND CONCLUSION:(1)A total of 32 active components of Modified Erxian Pill were identified,and 21 components entered the blood.The main components into blood included a variety of sesquiterpenoids.(2)Molecular docking results showed that 3-O-Acetyl-13-deoxyphomenone,Incensol oxide,Atractylenolide III,Rupestonic acid,and 3,7-Dihydroxy-9,11-eremophiladien-8-one had good binding activity with NLRP3.(3)Compared with the blank control group,lactate dehydrogenase activity and the expression levels of interleukin-1β and interleukin-18 were significantly increased in cell supernatant of lipopolysaccharide+adenosine triphosphate group(P<0.001).Hoechst/PI staining showed that the number of PI-positive cells was significantly increased.After the intervention of lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill group,all of them showed different degrees of reduction.(4)Compared with the blank control group,NLRP3,Caspase-1,GSDMD,and GSDMD-N protein expression levels were significantly increased in the lipopolysaccharide+adenosine triphosphate group(P<0.05).Compared with lipopolysaccharide+adenosine triphosphate group,the protein expressions of NLRP3,Caspase-1,GSDMD,and GSDMD-N were significantly decreased in the lipopolysaccharide+adenosine triphosphate+Modified Erxian Pill group(P<0.05),and had a certain dose dependence.These findings verify that the drug-containing serum of Modified Erxian Pill may inhibit the pyroptosis of J774A.1 macrophages by regulating the NLRP3/Caspase-1/GSDMD pathway.

Background/Aims: Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA). Methods: Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC). Results: The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively). Conclusions We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.

Background/Aims: Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA). Methods: Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC). Results: The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively). Conclusions We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.

In September 2023， the Measures for Scientific and Technological Ethics Review （Trial Implementation） was issued， revising the provisions related to the simplified procedure for ethical review in Chapter 3， Section 3. This revision of these provisions provides systematic guarantees for further optimizing ethical review work， ensuring that ethical review procedure is well-regulated， and improving scientific research efficiency. The “simplified procedure” does not mean reducing the quality and requirements of the review. Instead， based on always following internationally recognized ethical standards and emphasizing not violating national laws and regulations， improving the efficiency of ethical review and subsequent research work， and promoting the development of life sciences and medical research involving humans. In practical work， it introduces numerous new opportunities and challenges for the improvement of ethics review ability， such as new tests on the judgment and decision-making power of ethics committees， how to ensure the reliability and controllability of the conditions related to the simplified review procedure， and how to determine the basic conditions for adopting the simplified review procedure for review. Therefore， to actively respond to the challenges and possible risks brought by the simplified procedure review， efforts should be made to achieve three “unifications”， including the unification of researchers’ moral autonomy and the heteronomy of supervision implemented by relevant departments； the unification of the standard formulation of the simplified procedure review and the review work in practice； and the unification of ethical responsibility and legal responsibility.

Background/Aims: Early detection and effective prognosis prediction in patients with hepatocellular carcinoma (HCC) provide an avenue for survival improvement, yet more effective approaches are greatly needed. We sought to develop the detection and prognosis models with ultra-sensitivity and low cost based on fragmentomic features of circulating cell free mtDNA (ccf-mtDNA). Methods: Capture-based mtDNA sequencing was carried out in plasma cell-free DNA samples from 1168 participants, including 571 patients with HCC, 301 patients with chronic hepatitis B or liver cirrhosis (CHB/LC) and 296 healthy controls (HC). Results: The systematic analysis revealed significantly aberrant fragmentomic features of ccf-mtDNA in HCC group when compared with CHB/LC and HC groups. Moreover, we constructed a random forest algorithm-based HCC detection model by utilizing ccf-mtDNA fragmentomic features. Both internal and two external validation cohorts demonstrated the excellent capacity of our model in distinguishing early HCC patients from HC and highrisk population with CHB/LC, with AUC exceeding 0.983 and 0.981, sensitivity over 89.6% and 89.61%, and specificity over 98.20% and 95.00%, respectively, greatly surpassing the performance of alpha-fetoprotein (AFP) and mtDNA copy number. We also developed an HCC prognosis prediction model by LASSO-Cox regression to select 20 fragmentomic features, which exhibited exceptional ability in predicting 1-year, 2-year and 3-year survival (AUC=0.8333, 0.8145 and 0.7958 for validation cohort, respectively). Conclusions We have developed and validated a high-performing and low-cost approach in a large clinical cohort based on aberrant ccf-mtDNA fragmentomic features with promising clinical translational application for the early detection and prognosis prediction of HCC patients.

A case of idiopathic hypertrophic spinal pachymeningitis is reported. The patient was a middle-aged female, with the course of disease more than 1 year. Clinical manifestations included recurrent fever,headache and backache, and the magnetic resonance imaging showed diffuse enhancement and thickening of the spinal dura mater. Dural biopsy pathology finally confirmed hypertrophic spinal pachymeningitis. After treatment with surgery and immunotherapy, the patient′s clinical symptoms improved.

The clinical data of a case of Niemann-Pick disease type C diagnosed at Beijing Children′s Hospital, Capital Medical University on December 22, 2017 were retrospectively analyzed.The patient, male, 1 year and 28 days old, was admitted to the hospital primarily due to intermittent fever, cough and dyspnea for 8 months, and hepatosplenomegaly for 20 days.The patient initially presented with cough, expectoration, and wheezing, followed by hypotonia and delayed motor development.At the age of 1 year, the child developed hepatosplenomegaly and diffuse interstitial changes in both lungs.At the age of 3 years, the child had obvious vertical supranuclear gaze palsy and gelastic cataplexy, followed by dysarthria and dysphagia.The foam cells were found by bone marrow cytology, while sphingomyelinase and glucocerebrosidase were normal, so Niemann-Pick disease type A/B and Gaucher disease were excluded.Finally, genetic testing revealed two pathogenic mutations in the NPC1 gene, so Niemann-Pick disease type C was confirmed.Miglustat treatment began when the child was 3 years old, and vertical supranuclear gaze palsy and gelastic cataplexy improved for a while, but then the neurological symptoms worsened again, with dysphagia and dyspnea gradually increasing, and finally he died at the age of 4 years and 11 months.

Objective: To investigate the osteogenic effect of β-tricalcium phosphate (β-TCP) and bone morphogenetic protein-2 (BMP-2) in the repair of the alveolar cleft. Methods : Fifty-nine patients with unilateral alveolar cleft who visited Capital Medical University School of Stomatology from January 2016 to May 2021 were included. They were divided into three groups according to the different bone repair materials: autologous bone, β-TCP and BMP-2 +β-TCP. The preoperative and postoperative CBCT data of the patients were imported into Mimics 21.0 software. The preoperative volume of the bone defect and the new volume of bone formation were calculated by the three-dimensional reconstruction method. The osteogenesis rate was calculated to evaluate the osteogenesis effect Results: The wounds in the three groups healed well after the operation, without implant material discharge, infection, dehiscence, rejection or other symptoms. Twelve months after the operation, CBCT scanning and three⁃dimensional reconstruction images of the three groups of patients showed the formation of new bone bridges in the alveolar ridge fissure area. The image density of the new bone tissue was not significantly different from that of normal bone tissue, and the continuity of the maxilla was re⁃ stored to varying degrees. The bone rate of autogenous bone was 65.00% ± 16.66%, β⁃ TCP group and BMP⁃2+ β⁃ The bone composition rate of TCP was 69.82% ± 17.60%, 71.35% ± 17.51%, respectively, and there was no significant dif⁃ ference compared with the autogenous bone group (P = 0.382, P = 0.244). The β⁃TCP and BMP⁃2+ β⁃TCP groups had no significant differences in bone rate (P = 0.789). Conclusion β⁃TCP could be used to replace autologous bone for alveolar cleft repair. The addition of BMP⁃2 to β⁃TCP did not significantly improve the osteogenesis rate.

Objective:To evaluate the significance of copy number variation (CNV) and metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) in the diagnosis of meningeal carcinomatosis (MC).Methods:Ten patients with MC diagnosed in the Department of Neurology of Peking Union Medical College Hospital from March 2022 to June 2022 were consecutively enrolled in this study. The patients were diagnosed according to the criteria of the Chinese expert consensus on the diagnosis of MC by the Chinese Society of Infectious Diseases and Cerebrospinal Fluid Cytology, and the diagnosis of MC was confirmed by CSF cytology. The control group included 10 patients who were diagnosed as autoimmune encephalitis or viral encephalitis. CSF mNGS and CNV analysis were performed simultaneously in all the patients.Results:Of the 10 patients with MC, 6 had lung adenocarcinoma, 4 had breast cancer. CSF mNGS and CNV analysis detected large CNV in 8 of 10 patients with MC, including 4 patients with breast cancer and 4 patients with lung cancer. The results of pathogenic microorganism analysis of CSF mNGS in all the patients were negative. Meanwhile, large CNV was not detected in the control group.Conclusions:CSF CNV can serve as a diagnostic marker for MC. The combination of mNGS and CNV analysis has demonstrated a high positive rate in the diagnosis of MC. The dual-omics analysis of pathogenic microorganisms and CNV has been proposed as a potential strategy to further expand the clinical utility of CSF mNGS in the realm of auxiliary diagnosis.

Objective To explore the distribution of common syndromes in sepsis based on literature data mining.Methods The literature related to sepsis symptoms analysis included in China National Knowledge Infrastructure(CNKI),Chinese Biomedical Literature Database(CBM),VIP database(VIP)and Wanfang Data were searched by computer to extract relevant information and establish a database.Analysis of common syndromes and symptoms of sepsis by frequency statistics.Based on LTM-EAST algorithm of two-step hidden tree analysis,a symptom hidden structure model with frequency≥10 was constructed by Latern 5.0 software,and potential syndromes were inferred through comprehensive clustering.Symptoms with frequency＞5%were selected for factor analysis,common factors were extracted for further systematic cluster analysis,and potential syndromes were inferred according to the results.Based on the above results,the common syndromes and clinical characteristics of sepsis were analyzed.Results A total of 792 literatures and 961 syndromes records and 877 symptoms records were included,involving 48 syndromes after the regulation,with high frequency of pattern of blood stasis,pattern of yangming fu-organ excess,pattern of internal block of the heart orifices due to phlegm and heat,pattern of yang prostration,etc.The frequencies were 12.70%(122/961),9.68%(93/961),9.47%(91/961)and 7.80%(75/961).It involved 179 symptoms after the regulation,including high fever,red tongue,thirst,dysphoria,etc.The frequencies were 27.82%(244/877),27.36%(240/877),27.25%(239/877),25.54%(244/877).Forty-three hidden variables were obtained through implicit structure analysis,according to professional knowledge,12 potential syndromes were obtained by comprehensive clustering,including pattern of blood stasis,pattern of yangming fu-organ excess,pattern of phlegm and heat congesting in the lung,pattern of fire toxin entering the nutrient phase,pattern of Yin deficiency with exuberant heat,pattern of Yang prostration,pattern of Qi deficiency,pattern of Yang deficiency,pattern of turbid phlegm obstructing the lung,pattern of damp-heat encumbering the spleen,pattern of intense exuberant heat toxin,pattern of pathogenic factors repressing defensive Qi of lung.Twenty-five common factors were obtained by factor analysis,and 12 potential syndromes were inferred by systematic clustering,including pattern of heart-Yang deficiency,pattern of phlegm and heat congesting in the lung,pattern of yangming fu-organ excess,pattern of Yang prostration,pattern of intense exuberant heat toxin,pattern of Yang deficiency in spleen and kidney,pattern of Qi deficiency,pattern of phlegm and heat damaging Yin,pattern of Qi deficiency with blood stasis,pattern of Qi and Yin deficiency,pattern of pathogenic factors repressing defensive Qi of lung,and pattern of heat sinking into the pericardium.According to the standard of common traditional Chinese medicine(TCM)syndromes and their symptom characteristics,9 common syndromes of sepsis were finally obtained,including pattern of intense exuberant heat toxin,blood stasis,pattern of yangming fu-organ excess,pattern of phlegm and heat congesting in the lung,pattern of fire toxin entering,pattern of pathogenic factors repressing defensive Qi of lung,pattern of Qi and Yin deficiency,pattern of Qi deficiency,pattern of Yang prostration.Conclusion The symptoms and characteristics of common syndromes of sepsis are significant,which can provide evidence for the syndrome diagnosis standard of sepsis.